A-delta and C fiber sensory nerves make us aware of the environment (tactile and thermal sensation), are used for homeostatic regulatory mechanisms, mediate neurotrophic processes, and warn us of impending injury (irritation and pain). Alteration in the normal .physiology of these nerves can result in abnormal sensation, chronic pain and inadvertent injury in man. Despite their importance, little is known about the physiology of these sensory nerves, especially the mechanisms they use to transduce energy. In this proposal, rabbit corneal nerves will be studied using anatomic, electrophysiologic and pharmacologic techniques. The cornea is avascular, nonkeratinized, relatively homogeneous and innervated by only A-delta and C-fibers which terminate as unspecialized 'free' nerve terminals. It is an ideal tissue in which to study peripheral sensory mechanisms since in allows simultaneous visualization and electrophysiologic recording from sensory nerve terminals. In vivo and in vitro cornea preparations have been developed in this laboratory and electrophysiologically characterized. Molecular transduction mechanisms of the four corneal receptor types (mechanical, thermal, chemical and bimodal ) will be studied using, specific ion channel toxins; as well as, antibodies and Probes that interfere selectively with components of second messenger cyclic nucleotide and G-protein systems. The effects of tissue injury and nerve regeneration on spontaneous impulse generation, sensory threshold level, receptor specificity and response characteristics will be determined. Quantitative mechanical, thermal and chemical stimulation will be used to investigate the effects of anesthetics and analgesics on peripheral A-delta and C-fibers. Since the cornea has both sensory and sympathetic innervation, it also holds potential as a model of causalgia and reflex sympathetic dystrophy. Results of these studies will contribute to an understanding of the peripheral nervous systems role in the generation of normal and abnormal sensation including pain. This corneal nerve preparation will provide a system for designing and testing new pharmacologic agents to treat sensory nerve dysfunction.